Compositions and methods for diagnosing and treating cancer
An isolated antibody that specifically binds to an extracellular domain of human DLL4 and affects growth of a tumor comprising cancer stem cells is described. Also described is a method of treating cancer comprising administering a therapeutically effective amount of an anti-DLL4 antibody.
1. A monoclonal antibody that specifically binds human delta-like ligand 4 (DLL4) (SEQ ID NO:25), wherein the antibody binds the same epitope as that of antibody 21M18 produced by the hybridoma deposited with ATCC having deposit no. PTA-8670.
2. The monoclonal antibody of claim 1 , which is a humanized antibody.
3. The monoclonal antibody of claim 1 , which is a chimeric antibody.
4. The monoclonal antibody of claim 1 , which is a bispecific antibody.
5. The antibody of claim 1 , which is an IgG1 antibody.
6. The antibody of claim 1 , which is an IgG2 antibody.
7. The antibody of claim 1 , which inhibits tumor growth.
8. The antibody of claim 7 , wherein the tumor is colon tumor.
9. The antibody of claim 1 , which reduces cancer stem cell frequency in a solid tumor.
10. The antibody of claim 1 , which has a KD of about 0.1 μM or less.
11. The monoclonal antibody of claim 1 , which is an antigen binding antibody fragment.
12. The monoclonal antibody of claim 1 , which blocks Notch binding to human DLL4.
13. The monoclonal antibody of claim 1 , which blocks DLL4-mediated Notch signaling.
14. A pharmaceutical composition comprising the antibody of claim 1 and a pharmaceutically acceptable carrier.